Ubiquitin is highly conserved 76 amino acid protein found in all eukaryotic organisms and ubiquitin-proteasome pathway (UPP) plays a very important role in regulated non-lysosomal ATP dependent protein degradation. This pathway participates in or regulates numerous cellular processes, such as selective protein degradation, cell cycle progression, apoptosis, signal transduction, transcriptional regulation, receptor control by endocytosis, immune response and the processing of antigens. Nevertheless, roles of UPP in virus infection are only beginning to be clarified. Ubiquitin homology has also been found in insect viruses. All viral ubiquitin genes encode an N-terminal ubiquitin sequence and 3-256 amino acids C-terminal peptides. Most of the residues known to be essential for ubiquitin function have been conserved in the viral variant. In Autographa californica nucleopolyhedrovirus (AcMNPV), viral ubiquitin is attached to the inner surface of budded viron membrane by a covalently linked phospholipid and is not essential for viral replication. Currently, insect viruses are the only viruses known to encode ubiquitin. However, ubiquitin also plays a role in the life cycle of other viruses. Host ubiquitin molecules have been found in some plant viruses and other animal viruses. Additionally, Africa swine fever virus (ASFV) encodes a ubiquitin-conjugating enzyme (E2) and a putative causal link between human immunodeficiency virus type 1 (HIV-1) and ubiquitin was established by showing that depletion of the intracellular pool of free ubiquitin inhibits the virus budding. Further analyses indicated that many retroviruses proteins which are required for efficient pinching off the virus bud contain a late domain. The core element of the late domain is a proline-rich motif (PPXY) which mediates the late domain to be ubiquitinated by cellular proteins. Recently, it has been shown that many retroviruses have developed mechanisms to escape the cellular immune response, to facilitate virus replication and to promote virus assembly and budding via host UPP.
African Swine Fever Virus ; metabolism ; pathogenicity ; Animals ; Humans ; Insect Viruses ; metabolism ; pathogenicity ; Proteasome Endopeptidase Complex ; metabolism ; Retroviridae ; metabolism ; pathogenicity ; Ubiquitin ; metabolism ; Ubiquitin-Protein Ligase Complexes ; metabolism ; Virus Diseases ; virology ; Viruses ; pathogenicity

Objective To develop the scale of volume-management for peritoneal dialysis(PD) patients.Methods The item pool was formulated based on literature review and in-depth interviews.An initial scale was constructed through two rounds of Delphi expert consultation and preliminary test.Totally 125 PD patients from Jiangsu-Zhejiang-Shanghai area were investigated to test the reliability and validity of the scale.Results 2 factors were extracted by exploratory factor analysis,which contained 8 items and could explain 66.07％ of the total variance.The content validity index was 1.0,the Cronbach α was 0.870,and test-retest reliability was 0.930.Conclusions The scale is proved to be a reliable and valid tool for the volume-management assessment of PD patients.

Objective To investigate the status quo and influencing factors of self-management ability in patients undergoing continuous ambulatory peritoneal dialysis (CAPD).Methods Totally 339 CAPD patients with clinical follow-up regularly were investigated for the situation of self-management with general information questionnaire and Self-management Scale for CAPD.Results The total score of patients' self-management ability was (66.03±15.57).Multiple linear regression analysis showed that education level,marital status,occupation and duration of dialysis were influencing factors of patients' self-management ability.Conclusions Patients undergoing CAPD have certain degree of self-management ability.Nurses should promote their self-management ability according to different education level,marital status,occupation and duration of dialysis.

Objective To study the effects of ibuprofen on the growth and development of oligodendrocytes. Methods A total of 6 clean and healthy adult female SD (Sprague Dawley) rats were used for extracting and culturing of oligodendrocytes(OLs).Lysophosphatidic acid(LPA)was then added,and the morphological changes of OLs pre-treatment and post-treatment were observed. Then 6 newborn rats (born 24-48 h) were used for mixed glial cell extraction from the cortex, then the OPCs were inoculated into the culture plates and randomly divided into control group, ibuprofen group, lysophosphatidic acid(LPA)group and LPA+ibuprofen group.After the adhering of the cells in each group for three days, cell morphology was observed,and the drugs were added as interventions.The control group was treated with normal saline, and the other 3 groups were added with saline solution of ibuprofen(100 μmol/L),LPA(1.0 μmol/L)and the mixture of them. The cell morphological changes were observed after 7-day intervention.The morphology of OPCs and OLs were observed by immunofluorescence staining through OPCs'specific immune markers (platelet-derived growth factor receptor alpha, PDGFR-α)and OLs'specific immune markers(myelin basic protein,MBP)along with cell count of mature OLs.Western blot assay was used to detect the relative expression level of MBP in each group. Results After the treatment with LPA to the mature OLs,protrusions were shrinking and became very sparse.The morphology of cells developed well in each group after cell adhering for 3 days. After drug intervention for 7 days, more cell protrusions and branches were observed in ibuprofen group and LPA+ibuprofen group than those of the control group and LPA group.The results of cell count showed that the number of MBP positive cells was significantly higher in the ibuprofen group and LPA+ibuprofen group than that in the control group and LPA group(P<0.01).The results of Western blot assay showed that the MBP protein expression was significantly less in LPA group than the other three groups (P<0.01), and the expression was significantly higher in the ibuprofen group than that of LPA+ibuprofen group (P<0.01). Conclusion LPA has a toxic effect on the growth and development of OPCs, and it has an inhibitory effect on the normal growth of mature OLs. A certain concentration of ibuprofen can significantly inhibit the cytotoxicity of LPA on OPCs and OLs,and promote the formation and maintenance of mature OLs.

PURPOSETo investigate the potential correlation between two different types of hip fractures and serum calcium levels.

METHODSWe consecutively studied 101 cases of femoral neck fracture and 95 cases of femoral inter- trochanteric fracture between January 2011 and December 2013. Fasting blood samples were taken and serum calcium measurements were performed respectively in three periods: the time of admission, postoperation, and discharge. Creatinine, alkaline phosphatase and albumin were also analyzed.

RESULTSConsidering the levels of serum calcium between two groups at the time of admission, post- operation and discharge, there was significant difference at admission and discharge (p <0.05), while there was no significant difference at the time of postoperation (p > 0.05). The magnitude of serum calcium fluctuation was larger in femoral neck group than femoral intertrochanteric group. Concerning alkaline phosphatase and albumin levels at admission, there was no significant difference between two groups (p > 0.05).

CONCLUSIONThe capability of reservation and restoration of serum calcium in patients with femoral neck fracture is better than that in patients with femoral intertrochanteric fracture. A low serum calcium level may be susceptible to femoral intertrochanteric fracture.

Aged ; Aged, 80 and over ; Alkaline Phosphatase ; blood ; Calcium ; blood ; Female ; Hip Fractures ; blood ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Serum Albumin ; analysis

OBJECTIVETo reveal the sequence variations of the full coding region of the human alpha (1,beta/1,4) fucosyltransferase 5 gene (FUT5) in a Chinese Han population.

METHODSThe whole coding region of the FUT5 gene was amplified and sequenced in a total of 30 unrelated Chinese Han individuals. The PCR products containing the nucleotide variants observed in the study were subcloned into plasmid pcDNA to determine all potential haplotypes in the investigated population. Genetic polymorphisms of C560T (rs778970) and C484A loci were further analyzed by polymerase chain reaction-restriction fragment length polymorphism(PCR-RLFP) method.

RESULTSIn addition to seven previously reported base substitutions, two novel polymorphisms, namely C484A (Leu162Met) and T684C, were found in the coding region of the FUT5 gene in the 30 individuals. Seven haplotypes were identified by subcloning the variants into plasmid and subsequent DNA sequencing. The allele frequencies in the rs778970 locus in 160 Chinese Han individuals was 0.3031 for 560C and 0.6969 for 560T, while no polymorphism was detected in the C484A locus.

CONCLUSIONThe sequence of the coding region in the human FUT5 gene demonstrated high genetic diversity, and the allelic distribution of the rs778970 locus in the Chinese populations is polymorphic.

Alleles ; Asian Continental Ancestry Group ; ethnology ; genetics ; Base Sequence ; Fucosyltransferases ; genetics ; Gene Frequency ; Genetic Variation ; genetics ; Haplotypes ; Humans ; Open Reading Frames ; Polymorphism, Genetic ; Polymorphism, Single Nucleotide ; Population Groups ; genetics ; Sequence Analysis, DNA

OBJECTIVETo investigate the inhibitory effect on HBV replication of antisense locked nucleic acid (LNA) targeting to both S and C genes in HBV transgenic mice.

METHODSThirty HBV transgenic mice were randomly divided into five groups (n = 6): glucose control group were treated with 5% glucose solution, liposome control group were treated with liposome alone, S group were treated with LNA targeting to S gene, C group were treated with LNA targeting to C gene, and dual-target group were treated with LNA targeting to both S and C genes. Antisense LNA was injected into mice via the tail vein. Serum HBsAg was quantified by TRFIA. Serum HBV DNA was quantified by real-time PCR. The expression of HBV C-mRNA in the liver was detected by RT-PCR. The expression of HBsAg and HBcAg in the liver was detected by immunohistochemistry. Serum ALB, ALT, BUN and CR were measured using an automatic biochemical analyzer. The effects of antisense LNA on mouse organs were investigated by HE staining.

RESULTS5 days after LNA injection, serum HBsAg levels in the dual-target group were reduced by 72.8%, and serum HBV DNA levels were decreased by 52.9%. These values were significantly higher than those in the control groups (all P < 0.05). No significant differences were noted in serum ALB, ALT, BUN and CR between the experiment groups and the control groups (all P > 0.05). The expression levels of HBsAg and HBcAg in the liver of dual-target group were significantly lower than those in the control groups. No significant histopathological abnormality was found in liver and kidney tissues in all groups.

CONCLUSIONAntisense LNA targeting to both S and C genes can significantly inhibit HBV replication in transgenic mice.

Animals ; Antiviral Agents ; pharmacology ; DNA, Viral ; blood ; Female ; Hepatitis B Core Antigens ; analysis ; blood ; Hepatitis B Surface Antigens ; analysis ; blood ; Hepatitis B virus ; drug effects ; genetics ; physiology ; Immunohistochemistry ; Injections, Intravenous ; Liposomes ; Liver ; chemistry ; Male ; Mice ; Mice, Transgenic ; Oligonucleotides ; pharmacology ; Oligonucleotides, Antisense ; pharmacology ; Random Allocation ; Transcription, Genetic ; Virus Replication ; drug effects

OBJECTIVETo explore the relationship between the polymorphism of estrogen-biosynthesis genes (CYP17, CYP19, HSD17beta1) and risk of breast cancer.

METHODSA matched case-control study was designed. From May 2007 to July 2008, 200 pairs of subjects with and without breast cancer were enrolled, who were matched by age and menstruation status. Demographical characteristics, dietary factors and reproductive factors were investigated by questionnaire. CYP17 locus 1931 (T-->C), CYP19 codon 264 (Arg-->Cys) and HSD17beta1 locus 1954 (A-->G) were identified by AS-PCR (allele-specific PCR). The gene-gene interaction were analyzed with the MDR model (multifactor dimensionality reduction). Based on the results of MDR model, an unconditional logistic regression model was simulated to estimate the ORs of interaction factors and other risk factors.

RESULTSThe main effect of CYP17, CYP19 and HSD17beta1 susceptible genotypes were not correlated to breast cancer (OR approximately 1, P > 0.05). The positive interaction effect between CYP17 (T 1931C) and HSD17beta1 (A1954G) was discovered by MDR model with a statistically significant difference (Sign test, P = 0.05). The model's testing balance accuracy was 56.00%, and crossing validation consistency was 10/10. Multivariable unconditional logistic regression showed that after adjusting BMI, intake of estrogen, age of first birth, number of abortion and period of breast feeding, the interaction item of CYP17 (T1931C) and HSD17beta1 (A1954G) was strongly and positively correlated to breast cancer (OR = 2.52, 95%CI = 1.54 to 4.11).

CONCLUSIONThe estrogen-biosynthesis genes CYP17 (T1931C) and HSD17beta1 (A1954G) polymorphism may jointly increase the risk of breast cancer.

Aromatase ; genetics ; Breast Neoplasms ; genetics ; pathology ; Carcinoma, Ductal, Breast ; genetics ; pathology ; Case-Control Studies ; Estradiol Dehydrogenases ; genetics ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; Humans ; Logistic Models ; Polymorphism, Single Nucleotide ; Risk Factors ; Steroid 17-alpha-Hydroxylase ; genetics

Objective To investigate the safety and efficacy of endoscopic subserosal dissection (ESSD)for patients with upper gastrointestinal submucosal tumors. Methods A retrospective study was performed on the data of 6 patients with submucosal tumor undergoing ESSD in Nanjing Drum Tower Hospital from October 2016 to February 2017. The surgery time, surgical success rate, postoperative pathology and complications were analyzed. Results All patients successfully completed surgery. One patient had serosal perforation. The mean diameter of tumor was 27.5±10.0 mm. The mean surgery time was 49±18 min. The postoperative pathology of lesions was very low risk stromal tumor. No serious complications occurred. Conclusion ESSD is safe and reliable for patients with tumor originated from muscularis propria.

OBJECTIVETo evaluate the effect of titrated target-controlled infusion with propofol and remifentanil on anesthetics consumption and anesthesia depth in patients undergoing elective laparoscopic colorectal surgery.

METHODSSixty ASA I-III patients for elective laparoscopic colorectal surgery were enrolled. Titrated target-controlled infusion (TCI) with propofol and remifentanil was performed. Plasma concentration of the drugs was administered by titrated method to maintain bispectral index (BIS) in the range of 40-60 with systolic blood pressure (SBP) fluctuation within 20% of the basic value. BIS, SBP, plasma concentration of propofol and remifentanil were recorded at different time points. Awareness during operation was inquired postoperatively.

RESULTSDuring the entire anesthesia period, the blood pressure was stable and BIS was maintained less than 60. There was no awareness during operation. The plasma concentrations (95% confidence interval) for TCI of propofol and remifentanil were 2.55-2.65 mg/L and 4.09-4.26 μg/L respectively when existing surgical stimulation during anesthesia, and the plasma target concentration of propofol was lower than the recommended dosages.

CONCLUSIONTitrated target-controlled infusions with propofol and remifentanil for elective laparoscopic colorectal surgery can maintain proper anesthesia depth and reduce the drug consumption.

Adult ; Aged ; Aged, 80 and over ; Anesthesia, Intravenous ; methods ; Anesthetics, Intravenous ; administration & dosage ; Blood Pressure ; drug effects ; Colorectal Surgery ; Electroencephalography ; Female ; Humans ; Laparoscopy ; Male ; Middle Aged ; Piperidines ; administration & dosage ; Propofol ; administration & dosage